Artículos (Medicina)

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Incorporation mutational profile might reduce the importance of blast count in prognostication of low-risk myelodysplastic syndromes
(Wiley, 2024-08-28) García-Culebras, Marta; Alcalde, Patricia; Márquez Malaver, Francisco J.; Carrillo, Estrella; Soria, Elena; Prats, Concepción; Álvarez Morales, Rosario; Vargas de los Monteros, María Teresa; Pérez Simón, José Antonio; Falantes, Jose F.; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina
Addition of molecular data to prognostic models has improved risk stratification ofmyelodysplastic neoplasms (MDS). However, the role of molecular lesions, particu-larly in the group of low-risk disease (LR-MDS), is uncertain. We evaluated a set of227 patients with LR-MDS. Overall survival (OS) and probability of leukaemic pro-gression were the main endpoints. RUNX1 was associated with lower OS and SF3B1with a reduced risk of death (HR: 1.7, 95% CI, 1.1–2.9; p = 0.05; and HR: 0.23, 95% CI0.1–0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covari-ates for the probability of leukaemic progression (p < 0.001). Blast percentage, neitheranalysed as categorical (<5% vs. 5%–9%; HR: 1.3, 95% CI, 0.7–2.9; p = 0.2) nor as acontinuous variable (HR: 1.07, 95% CI, 0.9–1.1; p = 0.07), had impact on survival orprobability of progression (sHR: 1.05, 95% CI, 0.9–1.1; p = 0.2). These results retainedstatistical significance when analysis was restricted to the definition of LR-MDSaccording to the WHO 2022 and ICC classifications (<5% blasts). Thus, with theincorporation of molecular data, blast percentage happens to lose clinical signifi-cance both for survival and probability of progression in the group of patients withLR-MDS.
Impact of obesity‑associated myeloid‑derived suppressor cells on cancer risk and progression (Review)
(International journal of oncology; Espandidos Publications Ltd, 2024-06-27) Jiménez Cortegana, Carlos; Gutiérrez-García, Cristian; Sánchez Jiménez, Flora; Vilariño-García, Teresa; Flores-Campos, Rocío; Pérez Pérez, Antonio; Garnacho Montero, Carmen; García-Domínguez, Daniel J.; Cruz Merino, Luis de la; Sánchez Margalet, Víctor; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía; Universidad de Sevilla. CTS151: Bioquímica Medica; Universidad de Sevilla. CTS229: BioPatología Celular
Abstract. Obesity is a chronic disease caused by the accumulation of excessive adipose tissue. This disorder is characterized by chronic low grade inflammation, which promotes the release of proinflammatory mediators, including cytokines, chemokines and leptin. Simultaneously, chronic inflammation can predispose to cancer development, progression and metastasis. Proinflammatory molecules are involved in the recruitment of specific cell populations in the tumor microenvironment. These cell populations include myeloid derived suppressor cells (MDSCs), a heterogeneous, immature myeloid population with immunosuppressive abili ties. Obesity associated MDSCs have been linked with tumor dissemination, progression and poor clinical outcomes. A comprehensive literature review was conducted to assess the impact of obesity associated MDSCs on cancer in both preclinical models and oncological patients with obesity. A secondary objective was to examine the key role that leptin, the most important proinflammatory mediator released by adipo cytes, plays in MDSC driven immunosuppression Finally, an overview is provided of the different therapeutic approaches available to target MDSCs in the context of obesity related cancer.
Using network analysis to explore the validity and influential items of the Parkinson's Disease Questionnaire-39
(Nature Publishing Group; Nature Portfolio, 2023-05-03) Schönenberg, Aline; Santos García, Diego; Mir Rivera, Pablo; Wu, Jian Jun; Heimrich, Konstantin G.; Mühlhammer, Hannah M.; Prell, Tino; Universidad de Sevilla. Departamento de Medicina
Quality of life (QoL) in people with Parkinson´s disease (PD) is commonly measured with the PD questionnaire 39 (PDQ 39), but its factor structure and construct validity have been questioned. To develop effective interventions to improve QoL, it is crucial to understand the connection between different PDQ 39 items and to assess the validity of PDQ 39 subscales. With a new approach based on network analysis using the extended Bayesian Information Criterion Graphical Least Absolute Shrinkage and Selection Operator (EBICglasso) followed by factor analysis, we mostly replicated the original PDQ 39 subscales in two samples of PD patients (total N = 977). However, model fit was better when the “ignored” item was categorized into the social support instead of the communication subscale. In both study cohorts, “depressive mood”, “feeling isolated”, “feeling embarrassed”, and “having trouble getting around in public/needing company when going out” were identified as highly connected variables. This network approach can help to illustrate the relationship between different symptoms and direct interventional approaches in a more effective manner.
Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study
(Springer, 2021-04-13) Bond, Molly; Moll, Natalie; Rosello, Alicia; Bond, Rod; Schnell, Jaana; Burger, Bianka; Mir Rivera, Pablo; EMTICS (collaborative group); Universidad de Sevilla. Departamento de Medicina
This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36–0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD.
Biophysical evaluation of antiparallel triplexes for biosensing and biomedical applications
(Elsevier, 2024-02-29) Domínguez, Arnau; Gargallo, Raimundo; Cuestas Ayllón, Carlos; Grazu, Valeria; Fàbrega, Carme; Valiuska, Simonas; Noe, Véronique; Ciudad, Carlos J.; Calderón Sandubete, Enrique José; Martínez de la Fuente, Jesús; Eritja, Ramón; Aviñó, Anna; Universidad de Sevilla. Departamento de Medicina
Polypyrimidine sequences can be targeted by antiparallel clamps forming triplex structures either for biosensing or therapeutic purposes. Despite its successful implementation, their biophysical properties remain to be elusive. In this work, PAGE, circular dichroism and multivariate analysis were used to evaluate the properties of PPRHs directed to SARS-CoV-2 genome. Several PPRHs designed to target various polypyrimidine sites within the viral genome were synthesized. These PPRHs displayed varying binding affinities, influenced by factors such as the length of the PPRH and its GC content. The number and position of pyrimidine interruptions relative to the 4 T loop of the PPRH was found a critical factor, affecting the binding affinity with the corresponding target. Moreover, these factors also showed to affect in the intramolecular and intermolecular equilibria of PPRHs alone and when hybridized to their corresponding targets, highlighting the polymorphic nature of these systems. Finally, the functionality of the PPRHs was evaluated in a thermal lateral flow sensing device showing a good correspondence between their biophysical properties and detection limits. These comprehensive studies contribute to the understanding of the critical factors involved in the design of PPRHs for effective targeting of biologically relevant genomes through the formation of triplex structures under neutral conditions.
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
(Nature Research, 2024-02-19) Pérez Jurado, Luis A.; Cáceres, Alejandro; Balagué Dobón, Laura; Esko, Tonu; López de Heredia, Miguel; Quintela, Inés; Cruz, Raquel; Lapunzina, Pablo; Carracedo, Ángel; González, Juan R.; Calderón Sandubete, Enrique José; Universidad de Sevilla. Departamento de Medicina
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.
Novel risk loci for COVID-19 hospitalization among admixed American populations
(eLife Sciences Publications, 2024-10-03) Diz de Almeida, Silvia; Cruz, Raquel; Luchessi, Andre D.; Lorenzo Salazar, José M.; Heredia, Miguel López de; Quintela, Inés; Calderón Sandubete, Enrique José; Souto, Juan Carlos; Universidad de Sevilla. Departamento de Medicina; Gobierno de España; Cabildo Insular de Tenerife; Comunidad Autónoma de Canarias; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
Characteristics of clinical trials of influenza and respiratory syncytial virus registered in ClinicalTrials.gov between 2014 and 2021
(Frontiers Media, 2023-09-28) Lora Pablos, David; García Reyne, Ana; Lalueza, Antonio; Maestro de la Calle, Guillermo; Ruíz Ruigómez, María; Calderón Sandubete, Enrique José; Menéndez Orenga, Miguel; Universidad de Sevilla. Departamento de Medicina; European Union (UE); Instituto de Salud Carlos III
The randomized clinical trial (RCT) is the ideal and mandatory type of study to verify the effect and safety of a drug. Our aim is to examine the fundamental characteristics of interventional clinical trials on influenza and respiratory syncytial virus (RSV). This is a cross-sectional study of RCTs on influenza and RSV in humans between 2014 and 2021 registered in ClinicalTrials.gov. A total of 516 studies were identified: 94 for RSV, 423 for influenza, and 1 for both viruses. There were 51 RCTs of RSV vaccines (54.3%) and 344 (81.3%) for influenza virus vaccines (p < 0.001). Twelve (12.8%) RCTs for RSV were conducted only with women, and 6 were conducted only with pregnant women; for RCTs for influenza, 4 (0.9%) and 3, respectively. For RSV, 29 (31%) of the RCTs were exclusive to people under 5 years of age, and 21 (5%) for influenza virus (p < 0.001). For RSV, there are no RCTs exclusively for people older than or equal to 65 years and no phase 4 trials. RCTs on influenza virus and RSV has focused on vaccines. For the influenza virus, research has been consolidated, and for RSV, research is still in the development phase and directed at children and pregnant women.
Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease
(Baishideng Publishing Group Inc, 2018-12-14) Guerra Veloz, María Fernanda; Argüelles Arias, Federico; Laria, Luisa Castro; Maldonado Pérez, Belén; Benítez Roldán, Antonio; Perea Amarillo, Raúl; Merino Bohórquez, Vicente; Calleja, Miguel Ángel; Caunedo Álvarez, Ángel; Vilches Arenas, Ángel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
BACKGROUND Infliximab original has changed the natural history of inﬂammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.
The Impact of the Second Wave of the COVID-19 Pandemic on Non-COVID Hospital Care in a Tertiary Hospital in Spain
(MDPI, 2023-08-24) Gasch Illescas, Antonia; Andrade Arroyo, María; Vallejo Vaz, Antonio Javier; Praena Fernández, Juan Manuel; Guerrero, José A.; Calderón Sandubete, Enrique José; Pollán, Marina; Medrano Ortega, Francisco Javier; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla; Gobierno de España
In 2020, Spain ranked fourth among European countries with the highest excess mortality due to COVID-19 disease. This study evaluates the impact of the COVID-19 pandemic on non-COVID patients in a tertiary hospital during the second pandemic wave in Spain (22 June 2020–6 December 2020). Data from Virgen del Rocío University Hospital in Seville during that timeframe were compared with the data from the same period in the preceding two years (2018–2019). Between-group comparisons were performed using the Chi-squared test, Student’s t-test, or Mann–Whitney U tests, as appropriate. A total of 63,137 non-COVID patients were included in this study. During the second pandemic wave, a 19% decrease was observed in the annual number of non-COVID admissions overall (18,260 vs. 22,439, p < 0.001), but a 10% increase in the proportion of emergency admissions (60.6% vs. 54.93%, p < 0.001), a higher severity level of patients (1.79 vs. 1.72, p < 0.001), a longer in-hospital stay (7.02 vs. 6.74 days, p < 0.001), a 26% increase in non-COVID mortality (4.9% vs. 3.9%, p < 0.001), and a 50% increase in global mortality (5.9 vs. 3.9, p < 0.001) were also observed. In terms of both medical and surgical diagnoses, a significant reduction in the number of admissions and an increase in in-hospital mortality were observed. These results demonstrate the significant impact of the pandemic on hospital care, similar to what was previously observed during the initial wave in the same hospital. Our findings emphasize the need to include non-COVID patients when assessing the broad impact of the pandemic on healthcare, beyond its direct effects on COVID-19 patients.
Polimorfismo genético del correceptor CCR5 en pacientes cubanos VIH / SIDA de la tercera edad
(Editorial Ciencias Médicas, 2021-10) Hernández Requejo, Daymé; Franco Lacato, Alex Omar; Iglesias Pérez, Enrique; Calderón Sandubete, Enrique José; Armas Rodríguez, Yaxsier de; Universidad de Sevilla. Departamento de Medicina
Introducción: El 10 % de los infectados por VIH-1 son mayores de 50 años. La mutacióndel correceptor CCR5se relaciona con resistencia a la infección y con retraso en la progresión de la enfermedad. Objetivos: Identificar el polimorfismo genético del correceptor CCR5 en los pacientes VIH/sida de la tercera edad cubanos y evaluar su relación con el número de linfocitos T CD4+, la carga viral y las enfermedades oportunistas. Métodos: Se realizó un estudio de corte transversal en 45 pacientes atendidos en el Centro Hospitalario del IPK, durante los meses de enero a mayo de 2019. Para determinar el polimorfismo genético del correceptor CCR5 se realizó la reacción en cadena de la polimerasa. Resultados: El polimorfismo genético del correceptor CCR5 que predominó fue homocigótico salvaje 87%, con individuos con carga viral no detectable (80 %) y 56% niveles de linfocitos T CD4+ por encima de 350 cél/µl. La enfermedad oportunista que predominó fue la neumonía porPneumocystisjirovecii. No se observaron diferencias estadísticamente significativas, entre el polimorfismo genético del correceptor CCR5 y las variables estudiadas. Conclusiones:Primer estudio realizado en Cuba sobre el polimorfismo del correceptor CCR5 en pacientes VIH de la tercera edad que demuestra el limitado polimorfismo del gen. Estos resultados contribuyen al diseño de estrategias de tratamiento que mejoren la supervivencia estos pacientes.
Utilidad de la prueba de la lactato deshidrogenasa en fallecidos cubanos con SIDA y neumonía por Pneumocystis jirovecii
(Editorial Ciencias Médicas, 2021-07) Armas Rodríguez, Yaxsier de; Payne, Leston Iane; Menéndez Capote, Reinaldo L.; Poumier Suárez, Olga; Plascencia-Hernández, Arturo; Hernández-Cañaveral, Iván I.; Pérez Gómez, Héctor R.; Capó de Paz, Virginia; Calderón Sandubete, Enrique José; Universidad de Sevilla. Departamento de Medicina
Introducción: La neumonía por Pneumocystis jirovecii es una de las enfermedades de mayor impacto negativo en los pacientes con sida. La imposibilidad de cultivar el agente que la provoca, así como su cuadro clínico inespecífico y el alto costo de los métodos diagnósticos moleculares, señalan la necesidad de otras alternativas para su diagnóstico. La prueba de la lactato deshidrogenasa representa una opción a considerar. Objetivo: Demostrar la utilidad de la prueba de la lactato deshidrogenasa como diagnóstico de la Pneumocystis jirovecii en fallecidos cubanos por sida. Métodos: Se realizó un estudio de casos y controles (25 casos [Pneumocystis jirovecii] y 30 controles [compuestos por tres grupos: tuberculosis, linfoma y neumonía bacteriana, respectivamente]) en fallecidos cubanos a los que se realizó la autopsia desde enero de 1996 a diciembre de 2016. Se utilizaron cinco rangos de corte para buscar el valor óptimo de la prueba. Resultados: En el presente estudio existen diferencias altamente significativas entre los pacientes analizados (casos y controles) y entre los restantes individuos que componen los controles con respecto al del linfoma. El rango de corte óptimo para la prueba de la lactato deshidrogenasa fue (550-<800 U/I) con sensibilidad de 80 % y especificidad de 63 %. La razón de disparidad (OR) demostró que existe 6,91 veces más probabilidades que los pacientes por Pneumocystis jirovecii tengan las cifras de LDH mayor que los pacientes controles. Conclusiones: Este trabajo aporta evidencias científicas del rol de la prueba de la lactato deshidrogenasa como herramienta complementaria para el diagnóstico de la Pneumocystis jirovecii.
Hallazgos radiológicos de la neumonía por Pneumocystis jirovecii en fallecidos cubanos con VIH / SIDA
(Editorial Ciencias Médicas, 2020-05) Paz Bermúdez, Tania de la; García González, Idorkis; Capó de Paz, Virginia; Portela Ramírez, Daniel; Jiménez Pérez, Narciso A.; Calderón Sandubete, Enrique José; Armas Rodríguez, Yaxsier de; Universidad de Sevilla. Departamento de Medicina
Introducción: La neumonía por Pneumocystis jirovecii (PcP) es una de las enfermedades más frecuentes en los pacientes con VIH/sida y provoca una alta morbilidad y mortalidad. La radiología juega un papel fundamental para su diagnóstico presuntivo. Objetivo: Describir los hallazgos radiológicos de neumonía por Pneumocystis jirovecii en una serie de casos de fallecidos cubanos por VIH/sida, y relacionarlos con el estado inmunológico de los pacientes. Métodos: Se realizó el estudio de una serie de 69 fallecidos por sida con PcP en el Instituto de Medicina Tropical "Pedro Kourí” desde enero de 1996 a enero de 2014. El diagnóstico de la PcP se confirmó por estudios anatomopatológicos mediante la observación de estructuras compatibles con el hongo. Resultados: De los 69 casos del estudio, 57 (82,6 %) presentaron alteraciones en la radiografía de tórax. De ellos, 44 (77,2 %) y 13 (22,8 %) presentaron un patrón radiológico típico y atípico de la PcP, respectivamente. En 12 (17,4 %) fallecidos la radiografía de tórax fue normal. En 76,8 % de los casos se detectó niveles de linfocitos T CD4+ inferior a 200 cél/μL. La relación entre el patrón radiológico y el estado inmunológico de los fallecidos analizados no fue significativa. Conclusiones: Los hallazgos radiológicos descritos en los fallecidos cubanos por sida con PcP son similares a los informados en la literatura internacional. Sin embargo, el diagnóstico de la PcP no debe excluirse en pacientes con radiografías de tórax normales o con patrones atípicos que presenten un cuadro clínico sugestivo de la enfermedad.
Pneumocystis jirovecii in HIV patients and suspected pneumonia: a problematic diagnosis in Caracas, Venezuela
(Universidad del Zulia, 2021-01-13) Panizo, María Mercedes; Ferrara, Giuseppe; García, Nataly; Reviakina, Vera; Navas, Trina; Moreno, Xiomara; Capote, Ana María; Dolande, Maribel; Alarcón, Víctor; Calderón Sandubete, Enrique José; Universidad de Sevilla. Departamento de Medicina
Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in immunocompromised patients. The objective of this study was to know the P. jirovecii epidemiology in Venezuelan patients with Human Immunodeficiency Virus (HIV) infection and suspected pneumonia, through passive surveillance at a national reference laboratory during six years. Laboratory records of patients with HIV infection, who were hospitalized with acute lower respiratory tract infection (ALRTI), and presumptive clinical diagnosis of PCP, were reviewed between January 2007 and December 2012, at the Mycology Department of the Instituto Nacional de Higiene Rafael Rangel. Several respiratory specimens were received and the direct immunofluorescence assay (DIF) and nested polymerase chain reaction (nPCR) diagnostic techniques were used. One hundred and sixty-one respiratory samples were processed and P. jirovecii was detected in 76 samples by DIF and in 20 by nPCR. PCP’s frequency in Venezuelan patients with HIV is high and it has been sustained throughout time. Colonization by P. jirovecii has uncertain clinical significance, but this study provides evidence that the state of advanced immunosuppression increases the probability of colonization. DIF and nPCR are very useful techniques for PCP diagnosis, but are of limited access in many hospital centers, especially in developing countries. We recommend the use of DIF with spontaneous sputum specimens as the first diagnostic line for PCP in patients with HIV infection. The results obtained by nPCR should be interpreted with caution, taking into account the patient’s clinical symptoms.
Pneumocystis jirovecii in Patients With Cystic Fibrosis: A Review
(Frontiers Media, 2020-09-29) Bonnet, Pierre; Le Gal, Solène; Calderón Sandubete, Enrique José; Delhaes, Laurence; Quinio, Dorothée; Robert-Gangneux, Florence; Ramel, Sophie; Nevez, Gilles; Universidad de Sevilla. Departamento de Medicina
Pneumocystis pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those who have undergone an organ transplantation. Moreover, mild Pneumocystis jirovecii infections related to low pulmonary fungal burden, frequently designated as pulmonary colonization, occurs in patients with chronic pulmonary diseases, e.g., cystic fibrosis (CF). Indeed, this autosomal recessive disorder alters mucociliary clearance leading to bacterial and fungal colonization of the airways. This mini-review compiles and discusses available information on P. jirovecii and CF. It highlights significant differences in the prevalence of P. jirovecii pulmonary colonization in European and Brazilian CF patients. It also describes the microbiota associated with P. jirovecii in CF patients colonized by P. jirovecii. Furthermore, we have described P. jirovecii genomic diversity in colonized CF patients. In addition of pulmonary colonization, it appears that PCP can occur in CF patients specifically after lung transplantation, thus requiring preventive strategies. In other respects, Pneumocystis primary infection is a worldwide phenomenon occurring in non-immunosuppressed infants within their first months. The primary infection is mostly asymptomatic but it can also present as a benign self-limiting infection. It probably occurs in the same manner in CF infants. Nonetheless, two cases of severe Pneumocystis primary infection mimicking PCP in CF infants have been reported, the genetic disease appearing in these circumstances as a risk factor of PCP while the host-pathogen interaction in older children and adults with pulmonary colonization remains to be clarified.
Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes’ repertoires
(Nature Research, 2023-10-02) Meier, Caroline S.; Pagni, Marco; Richard, Sophie; Muhlethaler, Konrad; Almeida, João M.G.C.F.; Nevez, Gilles; Cushion, Melanie T.; Calderón Sandubete, Enrique José; Hauser, Philippe M.; Universidad de Sevilla. Departamento de Medicina; Swiss National Science Foundation (SNFS)
Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes.
Pneumocystis jirovecii in Spanish Patients With Heart Failure
(Frontiers Media, 2019-10-09) Merino Casallo, Izarbe; Friaza, Vicente; Menao, Sebastián; Domingo, José María; Olivera, Susana; Calderón Sandubete, Enrique José; Torralba, Miguel Ángel; Universidad de Sevilla. Departamento de Medicina; Red Iberoamericana sobre Pneumocystosis; Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (CYTED)
Objective: Pneumocystis colonization is frequent in patients with chronic obstructive pulmonary disease (COPD) producing local and systemic inflammation. Heart failure is also a common comorbidity among patients with COPD. Heart failure is a chronic, frequent, and disabling condition with high morbidity and mortality, but with a modifiable course where endothelial dysfunction and pulmonary arterial hypertension have great importance. Animal models have shown that Pneumocystis infection can cause relevant functionally changes in vascular responses in the lung, promoting the development of pulmonary hypertension. Pneumocystis colonization could be a hidden cause of worsening heart failure through it capacity to induce inflammatory response with subsequent endothelial dysfunction and pulmonary hypertension. The aim of the present study was to investigate the prevalence of Pneumocystis jirovecii colonization in heart failure patients and its possible association with reduced or preserved ejection fraction. Methods: A cross-sectional study was carried out including 36 heart failure patients and 36 control cases. Identification of P. jirovecii colonization was performed by means of molecular techniques in oropharyngeal washing. Results: Pneumocystis-DNA was identified in oropharyngeal washing in 1 (2.7%) of 36 heart failure patients and in 3 (8.3%) of 36 controls. Conclusions: Pneumocystis colonization does not seem to have a role in the pathophysiology of heart failure.
Congenital cytomegalovirus, parvovirus and enterovirus infection in Mozambican newborns at birth: A cross-sectional survey
(Public Library of Science, 2018-03-14) Madrid, Lola; Varo, Rosauro; Maculuve, Sonia; Nhampossa, Tacilta; Muñoz Almagro, Carmen; Calderón Sandubete, Enrique José; Bassat, Quique; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos III; Agencia Española de cooperación Internacional (AECI)
Background Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. Methods A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. Results From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. Conclusions This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings.
Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study
(Elsevier, 2017-06-29) Alanio, Alexandre; Gits-Muselli, Maud; Guigue, Nicolas; Desnos-Ollivier, Marie; Calderón Sandubete, Enrique José; Di Cave, David; Bretagne, Stéphane; Universidad de Sevilla. Departamento de Medicina
Pneumocystis jirovecii is an airborne human-specific ascomycetous fungus responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, affecting >500,000 patients per year (www.gaffi.org). The understanding of its epidemiology is limited by the lack of standardised culture. Recent genotyping data suggests a limited genetic diversity of P. jirovecii. The objective of the study was to assess the diversity of P. jirovecii across European hospitals and analyse P. jirovecii diversity in respect to clinical data obtained from the patients. Genotyping was performed using six already validated short tandem repeat (STR) markers on 249 samples (median: 17 per centre interquartile range [11−20]) from PCP patients of 16 European centres. Mixtures of STR markers (i.e., ≥2 alleles for ≥1 locus) were detected in 67.6% (interquartile range [61.4; 76.5]) of the samples. Mixture was significantly associated with the underlying disease of the patient, with an increased proportion in HIV patients (78.3%) and a decreased proportion in renal transplant recipients (33.3%) (p<0.001). The distribution of the alleles was significantly different (p<0.001) according to the centres in three out of six markers. In analysable samples, 201 combinations were observed corresponding to 137 genotypes: 116 genotypes were country-specific; 12 in two; six in three; and two in four and one in five countries. Nine genotypes were recorded more than once in a given country. Genotype 123 (Gt123) was significantly associated with France (14/15, p<0.001) and Gt16 with Belgium (5/5, p<0.001). More specifically, Gt123 was observed mainly in France (14/15/16 patients) and in renal transplant patient (13/15). Our study showed the wide population diversity across Europe, with evidence of local clusters of patients harbouring a given genotype. These data suggest a specific association between genotype and underlying disease, with evidence of a different natural history of PCP in HIV patients and renal transplant recipients.
Importance of tissue sampling, laboratory methods, and patient characteristics for detection of Pneumocystis in autopsied lungs of non-immunosuppressed individuals
(Springer, 2017-06-05) Vargas, S.L.; Ponce, C.; Bustamante, R.; Calderón Sandubete, Enrique José; Nevez, G.; de Armas, Y.; Matos, O.; Miller, R.F.; Gallo, M.J.; Universidad de Sevilla. Departamento de Medicina; Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). Chile; Comisión Nacional de Investigación Científica y Tecnológica (CONICYT). Chile
To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures, laboratory methodology, and patient characteristics of autopsy series reported in the literature. Number of tissue specimens, DNA-extraction procedures, age and underlying diagnosis highly influence yield and are critical to understand yield differences of Pneumocystis among reports of pulmonary colonization in immunocompetent individuals.

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